Landscape of immunogenic tumor antigens in successful immunotherapy of virally induced epithelial cancer

S Stevanović, A Pasetto, SR Helman, JJ Gartner… - Science, 2017 - science.org
S Stevanović, A Pasetto, SR Helman, JJ Gartner, TD Prickett, B Howie, HS Robins…
Science, 2017science.org
Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor
antigens targeted in successful treatments remain poorly defined. We used a personalized
immunogenomic approach to elucidate the global landscape of antitumor T cell responses
in complete regression of human papillomavirus–associated metastatic cervical cancer after
tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities
were directed against mutated neoantigens or a cancer germline antigen, rather than …
Immunotherapy has clinical activity in certain virally associated cancers. However, the tumor antigens targeted in successful treatments remain poorly defined. We used a personalized immunogenomic approach to elucidate the global landscape of antitumor T cell responses in complete regression of human papillomavirus–associated metastatic cervical cancer after tumor-infiltrating adoptive T cell therapy. Remarkably, immunodominant T cell reactivities were directed against mutated neoantigens or a cancer germline antigen, rather than canonical viral antigens. T cells targeting viral tumor antigens did not display preferential in vivo expansion. Both viral and nonviral tumor antigen–specific T cells resided predominantly in the programmed cell death 1 (PD-1)–expressing T cell compartment, which suggests that PD-1 blockade may unleash diverse antitumor T cell reactivities. These findings suggest a new paradigm of targeting nonviral antigens in immunotherapy of virally associated cancers.
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